Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: A Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25 + T lymphocytes

S. Audia, A. Nicolas, D. Cathelin, Nicolas Larmonier, C. Ferrand, P. Foucher, A. Fanton, E. Bergoin, M. Maynadie, L. Arnould, A. Bateman, B. Lorcerie, E. Solary, B. Chauffert, B. Bonnotte

Research output: Contribution to journalArticle

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Abstract

We determined the number and functional status of CD4+CD25 high regulatory T cells (Treg) in blood samples from patients with metastatic carcinoma, and evaluated their sensitivity to a single intravenous infusion of cyclophosphamide. Treg numbers were significantly higher in 49 patients with metastatic cancer (9.2% of CD4 + T cells) compared to 24 healthy donors (7.1%). These cells expressed the transcription factor forkhead box P3 (FoxP3), glucocorticoid- induced tumour necrosis factor receptor family-related protein (GITR) and intracellular CD152, and demonstrated a suppressive activity in vitro against CD4+CD25- autologous proliferation. At a single intravenous infusion, cyclophosphamide failed, in association with a non-specific immunotherapy by intratumoral bacille Calmette-Guérin (BCG), to modulate significantly Treg numbers or function. Metastatic cancer is associated with an expansion of peripheral blood CD4 +CD25highFoxP3+GITR+CD152 +Treg cells whose immunosuppressive properties do not differ from those of healthy subjects. Moreover, cyclophosphamide administration may not represent an optimal therapy to eliminate Treg, which further underlines the need to identify specific agents that would selectively deplete these cells.

Original languageEnglish (US)
Pages (from-to)523-530
Number of pages8
JournalClinical and Experimental Immunology
Volume150
Issue number3
DOIs
StatePublished - Dec 2007

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Clinical Trials, Phase I
Regulatory T-Lymphocytes
Immunotherapy
Cyclophosphamide
Carcinoma
T-Lymphocytes
Intravenous Infusions
Forkhead Transcription Factors
Tumor Necrosis Factor Receptors
Immunosuppressive Agents
Glucocorticoids
Neoplasms
Healthy Volunteers
Tissue Donors
Proteins
Therapeutics

Keywords

  • Immunotherapy
  • Metastatic carcinoma
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology

Cite this

Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma : A Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25 + T lymphocytes. / Audia, S.; Nicolas, A.; Cathelin, D.; Larmonier, Nicolas; Ferrand, C.; Foucher, P.; Fanton, A.; Bergoin, E.; Maynadie, M.; Arnould, L.; Bateman, A.; Lorcerie, B.; Solary, E.; Chauffert, B.; Bonnotte, B.

In: Clinical and Experimental Immunology, Vol. 150, No. 3, 12.2007, p. 523-530.

Research output: Contribution to journalArticle

Audia, S, Nicolas, A, Cathelin, D, Larmonier, N, Ferrand, C, Foucher, P, Fanton, A, Bergoin, E, Maynadie, M, Arnould, L, Bateman, A, Lorcerie, B, Solary, E, Chauffert, B & Bonnotte, B 2007, 'Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: A Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25 + T lymphocytes', Clinical and Experimental Immunology, vol. 150, no. 3, pp. 523-530. https://doi.org/10.1111/j.1365-2249.2007.03521.x
Audia, S. ; Nicolas, A. ; Cathelin, D. ; Larmonier, Nicolas ; Ferrand, C. ; Foucher, P. ; Fanton, A. ; Bergoin, E. ; Maynadie, M. ; Arnould, L. ; Bateman, A. ; Lorcerie, B. ; Solary, E. ; Chauffert, B. ; Bonnotte, B. / Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma : A Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25 + T lymphocytes. In: Clinical and Experimental Immunology. 2007 ; Vol. 150, No. 3. pp. 523-530.
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abstract = "We determined the number and functional status of CD4+CD25 high regulatory T cells (Treg) in blood samples from patients with metastatic carcinoma, and evaluated their sensitivity to a single intravenous infusion of cyclophosphamide. Treg numbers were significantly higher in 49 patients with metastatic cancer (9.2{\%} of CD4 + T cells) compared to 24 healthy donors (7.1{\%}). These cells expressed the transcription factor forkhead box P3 (FoxP3), glucocorticoid- induced tumour necrosis factor receptor family-related protein (GITR) and intracellular CD152, and demonstrated a suppressive activity in vitro against CD4+CD25- autologous proliferation. At a single intravenous infusion, cyclophosphamide failed, in association with a non-specific immunotherapy by intratumoral bacille Calmette-Gu{\'e}rin (BCG), to modulate significantly Treg numbers or function. Metastatic cancer is associated with an expansion of peripheral blood CD4 +CD25highFoxP3+GITR+CD152 +Treg cells whose immunosuppressive properties do not differ from those of healthy subjects. Moreover, cyclophosphamide administration may not represent an optimal therapy to eliminate Treg, which further underlines the need to identify specific agents that would selectively deplete these cells.",
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